The Ramsey property for operator spaces and noncommutative Choquet simplices

The noncommutative Gurarij space NG, initially defined by Oikhberg, is a canonical object in the theory of operator spaces. As the Fraisse limit of the class of finite-dimensional nuclear operator spaces, it can be seen as the noncommutative analogue of the classical Gurarij Banach space. In this paper, we prove that the automorphism group of NG is extremely amenable, i.e. any of its actions on compact spaces has a fixed point. The proof relies on the Dual Ramsey Theorem, and a version of the Kechris-Pestov-Todorcevic correspondence in the setting of operator spaces. Recent work of Davidson and Kennedy, building on previous work of Arveson, Effros, Farenick, Webster, and Winkler, among others, shows that nuclear operator systems can be seen as the noncommutative analogue of Choquet simplices. The analogue of the Poulsen simplex in this context is the matrix state space NP of the Fraisse limit A(NP) of the class of finite-dimensional nuclear operator systems. We show that the canonical action of the automorphism group of NP on the compact set NP1 of unital linear functionals on A(NP) is minimal and it factors onto any minimal action, whence providing a description of the universal minimal flow ofAut(NP). (C) 2021 Elsevier Inc. All rights reserved

Intraoperative goal directed hemodynamic therapy in noncardiac surgery: a systematic review and meta-analysis

Background: The goal directed hemodynamic therapy is an approach focused on the use of cardiac output and related parameters as end-points for fluids and drugs to optimize tissue perfusion and oxygen delivery. Primary aim: To determine the effects of intraoperative goal directed hemodynamic therapy on postoperative complications rates. Methods: A meta-analysis was carried out of the effects of goal directed hemodynamic therapy in adult noncardiac surgery on postoperative complications and mortality using Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology. A systematic search was performed in Medline PubMed, Embase, and the Cochrane Library (last update, October 2014). Inclusion criteria were randomized clinical trials in which intraoperative goal directed hemodynamic therapy was compared to conventional fluid management in noncardiac surgery. Exclusion criteria were trauma and pediatric surgery studies and that using pulmonary artery catheter. End-points were postoperative complications (primary) and mortality (secondary). Those studies that fulfilled the entry criteria were examined in full and subjected to quantifiable analysis, predefined subgroup analysis (stratified by type of monitor, therapy, and hemodynamic goal), and predefined sensitivity analysis. Results: 51 RCTs were initially identified, 24 fulfilling the inclusion criteria. 5 randomized clinical trials were added by manual search, resulting in 29 randomized clinical trials in the final analysis, including 2654 patients. A significant reduction in complications for goal directed hemodynamic therapy was observed (RR: 0.70, 95% CI: 0.62-0.79, p < 0.001). No significant decrease in mortality was achieved (RR: 0.76, 95% CI: 0.45-1.28, p = 0.30). Quality sensitive analyses confirmed the main overall results. Conclusions: Intraoperative goal directed hemodynamic therapy with minimally invasive monitoring decreases postoperative complications in noncardiac surgery, although it was not able to show a significant decrease in mortality rate

Association of common genetic variants with risperidone adverse events in a Spanish schizophrenic population

Risperidone non-compliance is often high due to undesirable side effects, whose development is in part genetically determined. Studies with genetic variants involved in the pharmacokinetics and pharmacodynamics of risperidone have yielded inconsistent results. Thus, the aim of this study was to investigate the putative association of genetic markers with the occurrence of four frequently observed adverse events secondary to risperidone treatment: sleepiness, weight gain, extrapyramidal symptoms and sexual adverse events. A series of 111 schizophrenia inpatients were genotyped for genetic variants previously associated with or potentially involved in risperidone response. Presence of adverse events was the main variable and potential confounding factors were considered. Allele 16Gly of ADRB2 was significantly associated with a higher risk of sexual adverse events. There were other non-significant trends for DRD3 9Gly and SLC6A4 S alleles. Our results, although preliminary, provide new candidate variants of potential use in risperidone safety prediction

Impact of CYP2C:TG Haplotype on CYP2C19 substrates clearance in vivo, protein content, and in vitro activity

A novel haplotype composed of two non-coding variants, CYP2C18 NM_000772.3:c.*31T (rs2860840) and NM_000772.2:c.819+2182G (rs11188059), referred to as “CYP2C:TG,” was recently associated with ultrarapid metabolism of various CYP2C19 substrates. As the underlying mechanism and clinical relevance of this effect remain uncertain, we analyzed existing in vivo and in vitro data to determine the magnitude of the CYP2C:TG haplotype effect. We assessed variability in pharmacokinetics of CYP2C19 substrates, including citalopram, sertraline, voriconazole, omeprazole, pantoprazole, and rabeprazole in 222 healthy volunteers receiving one of these six drugs. We also determined its impact on CYP2C8, CYP2C9, CYP2C18, and CYP2C19 protein abundance in 135 human liver tissue samples, and on CYP2C18/CYP2C19 activity in vitro using N-desmethyl atomoxetine formation. No effects were observed according to CYP2C:TG haplotype or to CYP2C19*1+TG alleles (i.e., CYP2C19 alleles containing the CYP2C:TG haplotype). In contrast, CYP2C19 intermediate (e.g., CYP2C19*1/*2) and poor metabolizers (e.g., CYP2C19*2/*2) showed significantly higher exposure in vivo, lower CYP2C19 protein abundance in human liver microsomes, and lower activity in vitro compared with normal, rapid (i.e., CYP2C19*1/*17), and ultrarapid metabolizers (i.e., CYP2C19*17/*17). Moreover, a tendency toward lower exposure was observed in ultrarapid metabolizers compared with rapid metabolizers and normal metabolizers. Furthermore, when the CYP2C19*17 allele was present, CYP2C18 protein abundance was increased suggesting that genetic variation in CYP2C19 may be relevant to the overall metabolism of certain drugs by regulating not only its expression levels, but also those of CYP2C18. Considering all available data, we conclude that there is insufficient evidence supporting clinical CYP2C:TG testing to inform drug therapyP.S.-C. is financed by Universidad Autónoma de Madrid (FPIUAM, 2021). P.Z. is financed by Universidad Autónoma de Madrid, Margarita Salas contract, grants for the requalification of the Spanish university system. A.R.-L. and E.G.-I. contracts are financed by Programa Investigo (NextGenerationEU funds of the Recovery and Resilience Facility), fellowship numbers 2022-C23.I01.P03. S0020–0000031 and 09-PIN1-00015.6/2022. Human liver tissue samples were obtained through the Liver Tissue Cell Distribution System, Minneapolis, MN, and Pittsburgh, PA, which was funded by NIH Contract #HHSN276201200017C. The proteomics part of the work was supported by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) Grant R01.HD08129

Quantification of inaccurate diagnosis of COPD in primary care medicine: An analysis of the COACH clinical audit

Background: Inaccurate diagnosis in COPD is a current problem with relevant consequences in terms of inefficient health care, which has not been thoroughly studied in primary care medicine. The aim of the present study was to evaluate the degree of inaccurate diagnosis in Primary Care in Spain and study the determinants associated with it. Methods: The Community Assessment of COPD Health Care (COACH) study is a national, observational, randomized, non-interventional, national clinical audit aimed at evaluating clinical practice for patients with COPD in primary care medicine in Spain. For the present analysis, a correct diagnosis was evaluated based on previous exposure and airway obstruction with and without the presence of symptoms. The association of patient-level and center-level variables with inaccurate diagnosis was studied using multivariate multilevel binomial logistic regression models. Results: During the study 4,307 cases from 63 centers were audited. The rate of inaccurate diagnosis was 82.4% (inter-regional range from 76.8% to 90.2%). Patient-related interventions associated with inaccurate diagnosis were related to active smoking, lung function evaluation, and specific therapeutic interventions. Center-level variables related to the availability of certain complementary tests and different aspects of the resources available were also associated with an inaccurate diagnosis. Conclusions: The prevalence data for the inaccurate diagnosis of COPD in primary care medicine in Spain establishes a point of reference in the clinical management of COPD. The descriptors of the variables associated with this inaccurate diagnosis can be used to identify cases and centers in which inaccurate diagnosis is occurring considerably, thus allowing for improvement